title: Treatment with pravastatin attenuates progression of chronic pancreatitis in rat.
abstract: As appropriate therapies for pancreatic fibrosis and inflammation are limited, prognosis of chronic pancreatitis has not improved to date. Recent studies have shown that statins improve inflammation and fibrosis in several organs. We therefore examined the therapeutic effect of pravastatin on progression of chronic pancreatitis by starting this treatment after induction of pancreatic fibrosis in rats. Chronic pancreatitis was induced by continuous pancreatic ductal hypertension (PDH) for 14 days according to our previous study. Pravastatin at a dose of 10 mg/kg/day was administrated directly into the duodenum via cannula from 2 days after induction of PDH. Progression of pancreatic fibrosis and expression levels of transforming growth factor-β1 and tumor necrosis factor-α mRNA were markedly attenuated after commencement of pravastatin compared with untreated group with PDH. In addition, pravastatin treatment markedly improved pancreatic exocrine function and significantly elevated expression level of interleukin (IL)-10 and superoxide dismutase activity in the pancreas compared with the untreated group with PDH. These results revealed that pravastatin substantially attenuates the progression of pancreatic inflammation, fibrosis and exocrine dysfunction probably by its anti-oxidative property and overproduction of IL-10 in animal model of chronic pancreatitis. These results provide an experimental evidence that pravastatin exerts beneficial effect for progression of chronic pancreatitis.
authors.affiliation: The Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan School of Medicine, Kitakyushu, Japan.
authors.forename: Limin
authors.initials: L
authors.lastname: Wei
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Masaru
authors.initials: M
authors.lastname: Harada
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuki
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D005355:Fibrosis; D006909:Hydroxyproline; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D050500:Pancreatitis, Chronic / Q000188:drug therapy*; D017035:Pravastatin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013482:Superoxide Dismutase; D017035:Pravastatin; D006909:Hydroxyproline